The objective of this project is to determine the functional significance of axon conduction blocks. This entails characterization of the physiological mechanisms and the anatomical substrate underlying action potential conduction blocks in the nervous system. To determine if conduction blocks occur in intact animals or if they are artifacts of an experimental preparation, the activity of a nerve in which propagation failure has been obsrved will be monitored in a freely moving animal. Using focal extracellular recordings of action potentials, the occurrence and the location of propagation failures will be registered; in addition, the diameters of the axonal branches in which this occurred will be measured using modulation-contrast and bright-field light microscopy. With these data, the relationship between axon branch size and time of occurrence of conduction failure can be analyzed. The ionic mechanisms underlying these phenomena in a preparation in which propagation is blocked will be elucidated by (1) examining the shape of the action potential recorded extracellularly, (2) varying the concentrations of sodium, calcium and potassium in the extracellular bath solution, and (3) monitoring extracellular potassium concentrations with ion-sensitive electrodes. In addition, features of the periaxonal environment which might contribute to conduction block, such as restricted extracellular space or reduced Schwann cell tissue, will be examined by electron microscopy.